They called it PUM, pseudouridimicine, and is a powerful new antibiotic, highly effective against resistant bacteria, discovered in Italian soil, between Bolgheri and San Guido (as rifampicin was discovered in the Cote d'Azur). Research has appeared on Cell's latest issue and may well be the turning point, but it will take years of studies and confirms to come to human use. The premise, however, is all there. They studied it at the Waksman Institute of Microbiology at Rutgers-New Brunswick, where in 1943 Albert Schatz and Samuel Waksman, a microbiologist, discovered the antibiotic for Tbc streptomycin (Waksman was awarded the Nobel Prize in 1952, the forgotten Schatz came Later rehabilitated).

MICROBES IN THE SOIL - Now PUM seems to remind us of the company of Italian scientists Lepetit with rifampicin, another antibiotic that is still used and decisive in the treatment of tuberculosis. They called it rifampicin (and so did the entire rifamycin group) because Italian microbiologists (Ermes Pagani, Piero Sensi and Maria Teresa Timbal) called Rififi, the title of a film, the ground samples of Saint Raphael, Cote d'Azur, Where they analyzed the microbes. Here, in addition to the great names of Rutgers (lead chemist Richard H. Ebright) we have two Italians from the University of Milan, Thomas Carzaniga ("I worked as a post-doc to the project") and the microbiologist Gianni Dehò, and an industry Biotechnology, Naicons srl, whose managing director is Stefano Donadio. Other Italians from Naicons, NeED Pharma Srl and Vicuron Pharmaceuticals Italy Srl participated (but also two Germans from the University of Bonn, Alina Iulia Chiriac and Hans-Georg Sahl); In addition, the Ministry of Research and the Lombardy Region contributed with funding. Donadio is the main co-author of the article on Cell, training in Naples, specialization in the USA (John Hopkins and Wisconsin), a past in pharmaceuticals (Abbott in Chicago and, incidentally, Lepetit in Italy), teaches at various universities pralarne. It is not new to the creation of companies, starting with Biosearch Italia (now the Allergan Group, based in Milan via Lepetit), or looking for new antibiotics, where it has contributed to the production process of Dalbavancin (antibiotic for skin) and now Is also at the head of the KtedoGen company that collaborates with Naicons in the search for new antibiotics

THE GREAT HISTORY OF PUM - Tells Donadio that the new antibiotic was discovered by a microorganism isolated from a sample of soil harvested in Italy ("in 1991 from a particularly significant location: it was actually collected under a cypress between Bolgheri and San Guido" , Says researcher Paolo Monciardini), under a program aimed at isolating particular microorganisms living in soil, called attinomicets, known for their ability to produce antibiotics. "In the period 1996-2005 in the laboratories Biosearch Italia of Gerenzano, then Vicuron Pharmaceuticals, some 45 thousand isolates were isolated, which are now part of the NAICONS collection," says Donadio. Rifampicin, isolated from the soil, is also part of the group of attinions. According to Donadio, there are "many similarities and some differences" with respect to the golden years of Lepetit and rifampicin. Both discovered by actinomycetes "act on the same target, polymerase RNA, but bonding to different sites." In the Gold Age of Antibiotic Research (1950-1970) were the major pharmaceuticals involved in research, now university centers and small companies. Each year, on the wave of the emerging antibiotic resistance problem, scientific articles of new discoveries appear: for example, three days ago on Scientific Reports and Antimicrobial Agents and Chemotherapy appeared a research by the University of Copenhagen of a group led by the Italian Luca I watch with an approach that exploits a genetic technique to attack resistant bacteria in Klebsiella pneumoniae and in Escherichia coli. Donadio tells more about Lepetit's discoveries: "an element of continuity is the fact that NAICONS is, if so desired, the continuation of Lepetit research laboratories, which later became Biosearch Italia."

ACTION MECHANISMS

"Rifamycin was discovered for its antibacterial activity and then its target was identified, while PUM was exactly the opposite," says Donadio, who explains why PUM looks more promising in the face of resistant mutations: " Rifampicin binds to the target, RNA polymerase, essential enzyme in the functions of all organisms and bacterium here, establishing contacts with 27 different amino acid residues, each of which can change, thus preventing rifampicin from binding and thus inhibiting the Enzyme (see drawing alongside, ndr), PUM binds only to many amino acid residues that can not be mutated without loss of enzymatic activity, and also binds to DNA and RNA, less the number of amino acids that can change while maintaining the 'Enzyme activity, the lower the frequency with which mutations that give drug resistance will arise.' The molecule - the researchers say - has been tested in an experimental model of mouse infection and has yielded satisfactory results. It could be a real breakthrough in the history of antibiotics, as has been the case with nucleoside analog inhibitors, which have revolutionized Hiv and Hepatitis C medicines. "But nothing is taken in medicine, Prudently add. Professor Dehò of the University of Milan: "Some of our experiments that have helped establish the mechanism of action and specificity have verified that PUM inhibits bacterial polymerase RNA but is much less active in the three RNA polymerases." The authors write on Cell: "PUM is the first analogous nucleoside inhibitor that selectively inhibits RNA polymerases, but not human ones." What it takes for an antibiotic, probably super.